Compositions and processes for preparing 5-amino or substituted amino 1,2,3-triazoles and triazoles orotate formulations
AssigneeTactical Therapeutics Inc
InventorRashida A. Karmali
Life of this patent
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Abstract
New polymorphs of 5-amino or substituted amino 1,2,3-triazole and substituted derivatives thereof, of orotates of the carboxyamidotriazoles, of formulations of the triazoles and orotic acid in the ratio of 1:1 to 1:4 (base:acid) and of safer processes of the preparation of the same are disclosed. The compounds are useful in the control and treatment of diseases including, but not limited to solid cancers, macular degeneration, retinopathy, chronic myeloid leukemia, AIDS and diseases which rely on aberrant signal transduction. The improved processes to prepare the orotate formulations use stable, efficient and safer starting azide intermediate materials in the synthesis of new polymorphs of carboxyamidotriazole.
Claims20
A polymorph form 1 of 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide obtainable by a process comprising:
- reacting diphenylphosphoryl azide with 3,5-dichloro-4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide;
- and
- reacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide.
A polymorph form 2 of 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide obtainable by a process comprising:
- reacting diphenylphosphoryl azide with 3,5-dichloro-4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide;
- and
- reacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide.
A polymorph form 1 of 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide obtainable by a process comprising:
- reacting diphenylphosphoryl azide with 3,5-dichloro-(4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide;
- reacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide;
- and reacting orotic acid with 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide bonded with orotic acid in which orotic acid is bonded in the range of 1:1 to 1:4.
A method of making polymorph form 1 of 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide comprising:
- reacting diphenylphosphoryl azide with 3,5-dichloro-4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide;
- reacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide;
- and
- reacting orotic acid with 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide.
A method of making polymorph form 1 of 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide bonded with orotic acid, wherein the orotic acid is ionically bonded in the range of 1:1 to 1:4 comprising:
- reacting diphenylphosphoryl azide with 3,5-dichloro-4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide;
- reacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide;
- and
- reacting orotic acid with 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide.
A polymorph form 2 of 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide obtainable by a process comprising:
- reacting diphenylphosphoryl azide with 3,5-dichloro-4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide;
- reacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide;
- and reacting orotic acid with 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide bonded with orotic acid in which orotic acid is bonded in the range of 1:1 to 1:4.
A method of making polymorph form 1 of 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide comprising:
- reacting diphenylphosphoryl azide with 3,5-dichloro-4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide;
- and
- reacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide.
A method of making polymorph form 1 of 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide bonded with orotic acid, wherein the orotic acid is ionically bonded in the range of 1:1 to 1:4 comprising:
- reacting diphenylphosphoryl azide with 3,5-dichloro-4-(4′-chlorobenzoyl)benzyl alcohol to obtain 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide;
- reacting 2-cyanoacetamide with 3,5-dichloro-4-(4-chlorobenzoyl)benzylazide to obtain 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide;
- and
- reacting orotic acid with 5-amino-1-(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide.
A compound comprising a polymorph form 1 of 5-amino-1-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide having a powder x-ray diffraction pattern comprising peaks at 2θ of 20.2, 24.3, 26.5 and 27.
A compound comprising a polymorph form 2 of 5-amino-1-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1,2,3-triazole-4-carboxamide having a powder x-ray diffraction pattern comprising peaks at 2θ of 19.2, 23.5, 24.6 and 28.3.
Dependencies are inferred from the claim text.